Metastaic Melanoma MedDRA version: 14.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MORAb-004
Product Code: MORAb-004
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: MORAb-004
Concentration unit: mg/ml milligram(s)/millilitre
Concentrati
Sponsors
Morphotek Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] At least 18 years of age [2] Surgically sterile or who consent to use a medically acceptable method of contraception throughout the study period [3] Histologically confirmed diagnosis of metastatic cutaneous (nonocular, nonmucosal) melanoma [4] At least one prior systemic treatment for metastatic melanoma with disease progression following treatment [5] Measurable disease, as defined by RECIST v.1.1, assessed within 4 weeks prior to study entry [6] Prior anticancer therapy (chemotherapy, immunotherapy, or radiation therapy) must have been completed at least 3 weeks (21 days) prior to starting MORAb-004 therapy, and all treatment-associated toxicity must be resolved to Grade 1 or less before the first infusion of study drug (MORAb-004) [7] Life expectancy of at least 3 months as estimated by the investigator [8] Any other significant medical conditions well-controlled and stable, in the opinion of the investigator, for at least 30 days prior to Study Day 1 [9] ECOG Performance Status of 0 or 1 at screening [10] Disease sites amenable to protocol-specified tissue biopsy (Note: All subjects will have protocol-specified biopsy at screening. The second, on-treatment biopsy will be required in the first 30 randomized subjects and is optional for all subsequently randomized subjects.)[11] Willingness and ability to provide written informed consent [12] Laboratory test results within 14 days prior to Study Day 1: Absolute neutrophil count at least 1.5×10^9/L; Platelet count at least 100 × 10^9/L; Hemoglobin at least 8 g/dL; Creatinine no greater than 1.5 × ULN (NCI CTCAE Grade 1); Bilirubin less than 1.5 × ULN (NCI CTCAE Grade 1); Aspartate aminotransferase and alkaline phosphatase less than 2.5 × ULN (NCI CTCAE Grade 1); Activated partial thromboplastin time (aPTT) and prothrombin time (PT) less than 1.5 × ULN (NCI CTCAE Grade 1) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 56 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: [1] No prior systemic treatment for metastatic melanoma [2] Evidence of active malignancy other than metastatic melanoma requiring treatment within the last 5 years (other than basal cell or squamous cell skin cancer) [3] Clinically significant heart disease [4] ECG demonstrating clinically significant arrhythmia [5] Any other serious systemic disease, including active bacterial or fungal infection, or any medical condition requiring cytotoxic therapy or chronic use of systemic corticosteroids (use for at least 4 consecutive weeks) [6] Active viral hepatitis or symptomatic HIV infection (Asymptomatic positive serology is not exclusionary.) [7] Breast-feeding, pregnant, or likely to become pregnant during the study [8] Known allergic reaction to a prior monoclonal antibody therapy [9] Previous treatment with MORAb-004 (anti-TEM-1) [10] Any evidence of brain metastasis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: [1] To evaluate the rate of Progression-Free-Survival (PFS) at 24 weeks of 2 dose levels of MORAb-004 in subjects with metastatic melanoma based on Response evaluation Criteria in Solid Tumors (RECIST) v 1.1;Secondary Objective: [1] To evaluate the Optimal Biological Dose (OBD) of MORAb-004 using a Pharmacokinetic (PK)/Pharmacodynamic (PD) model of drug activity [2] To correlate the pattern of TEM-1 expression in tumor samples with clinical parameters, including PFS [3] To assess the following additional clinical parameters: PFS over the course of the study, Overall survival (OS), Safety and tolerability of MORAb-004, and Tumor tissue-based and serum-based PD biomarkers;Primary end point(s): [1] PFS;Timepoint(s) of evaluation of this end point: 24 week PFS Imaging by MRI/CT: screening, D22 (even # cycles), final visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): [1] Radiologic PFS, including rate at 16 and 52 weeks [2] OS [3] ORR [4] Serum MORAb-004 concentrations [5] Serum marker of TEM-1 inhibition or other proteins in the TEM-1 pathway (potentially including platelet-derived growth factor, soluble galectin-3 or galectin-3-BP) [6] Tissue based markers of TEM-1 pathway, including TEM-1, galectin-3, fibronectin, mean pericyte index,leukocyte phenotyping, total vessel density, and total pericyte count and BRAF/NRAS mutation status. [7] Adverse events (AEs), including drug hypersensitivity reactions (DHAEs) [8] Clinical laboratory tests (serum chemistry, hematology, urinalysis) [9] Tolerability (discontinuations, treatment delays) [10] Physical examinations, including vital signs assessment and neurological examinations [11] Standard ECG assessments, including a clinical evaluation of prolongation of QTc interval [12] Human antihuman antibody (HAHA) assessment;Timepoint(s) of evaluation of this end point: 16 and 52 week PFS Imaging by MRI/CT: screening, D22 (even # cycles), final visit Disease assessment: screening, D22 (each cycle), final visit Serum-based PD biomarkers: screening, D1, D3-4, D15, D22 (cycle 1), D1, D15 (all subsequent cycles), final visit Biopsy: D1 (all subjects), D21-28 (first 30 subjects) Serum concentration of MORAb-004: D1, D3-4, D8, D15, D22 (cycle 1), D1, D15 (all subsequent cycles), final visit HAHA assessment: D1 and D15 (each cycle), final visit Clinical Labs: screening, D1 and D15 (each cycle), final visit Physical exam: screening, D1 (each cycle), the final visit Vital signs: screening, D1, D8, D15, D22 (each cycle), final visit AEs: each visit ECG: pre and post infusion D1, D22 (cycles 1 & 2) and during infusion D1 (cycle 3) | — |
Countries
Australia, Germany, United Kingdom, United States
Contacts
Public ContactMedical Information
Eisai Ltd
Outcome results
None listed